The Diamino-biphenyl-disulfonic acid oligomers of the present invention are able to inhibit enzymes that are actively involved in the degradation of connective tissues. Specifically, the diamino-biphenyl-disulfonic acid oligomers of the present invention are able to inhibit the activity of elastase and cathepsin G.
Elastase and cathepsin G are serine proteases found in the primary granules of human neutrophils that have the capacity to degrade numerous connective tissue macromolecules including elastin, fibronectin, collagen and proteoglycan. Because large numbers of neutrophils are present at sites of inflammation, neutrophil elastase and cathepsin G have been implicated in the tissue destruction associated with a number of diseases including adult respiratory distress syndrome, cystic fibrosis, acute bronchitis, emphysema and arthritis.
Normally the large quantities of endogenous protease inhibitors present in plasma and mucous secretions provide ample protection against connective tissue damage mediated by neutrophil proteolytic enzymes. However, when the balance between inhibitors and proteases is disturbed tissue damage may occur. When connective tissue proteases are left unchecked the effect is a deterioration of the underlying connective tissue. This effect may result from a host of initial causes of connective tissue destruction, including direct physical injury, aging, and genetic imbalances. For instance, individuals with a genetic deficiency resulting in reduced levels of the endogenous inhibitor, .alpha.-1-antitrypsin, have a strong tendency to develop emphysema at an early age thus further supporting the enzyme imbalance theory in connective tissue diseases.
An object of this invention is the use of diaminobiphenyl-disulfonic acid oligomers as inhibitors of elastase and cathepsin G. These inhibitors thereby provides an opportunity to control disease states associated with the degradation of these tissues.